Impact of age and cardiovascular risk factors on the incidence of adverse events in patients with rheumatoid arthritis treated with Janus Kinase inhibitors: data from a real-life multicentric cohort.

Inhibiting Janus Kinases (JAK) is a crucial therapeutic strategy in rheumatoid arthritis (RA). However, the use of JAK inhibitors has recently raised serious safety concerns. The study aims to evaluate the safety profile of JAKi in patients with RA and identify potential risk factors (RFs) for adverse events (AEs). Data of RA patients treated with JAKi in three Italian centers from January 2017 to December 2022 were retrospectively analyzed. 182 subjects (F:117, 64.3%) underwent 193 treatment courses. 78.6% had at least one RF, including age ≥ 65 years, obesity, smoking habit, hypertension, dyslipidemia, hyperuricemia, diabetes, previous VTE or cancer, and severe mobility impairment. We identified 70 AEs (28/100 patients/year), among which 15 were serious (6/100 patients/year). A high disease activity was associated with AEs occurrence (p = 0.03 for CDAI at T0 and T6; p = 0.04 for SDAI at T0 and T6; p = 0.01 and p = 0.04 for DAS28ESR at T6 and T12, respectively). No significant differences in AEs occurrence were observed after stratification by JAKi molecules (p = 0.44), age groups (p = 0.08) nor presence of RFs (p > 0.05 for all of them). Neither the presence of any RFs, nor the cumulative number of RFs shown by the patient, nor age ≥ 65 did predict AEs occurrence. Although limited by the small sample size and the limited number of cardiovascular events, our data do not support the correlation between cardiovascular RFs-including age-and a higher incidence of AEs during JAKi therapy. The role of uncontrolled disease activity in AEs occurrence should by emphasized.

Tocilizumab Vs Methotrexate in a Cohort of Patients Affected by Active GCA: A Comparative Clinical and Ultrasonographic Study.

Introduction: No head-to-head study has assessed the superiority of tocilizumab versus methotrexate in giant cell arteritis (GCA), and few studies have demonstrated its effectiveness in terms of ultrasonographic findings, but without a control group. The primary endpoint was to assess whether tocilizumab was superior to methotrexate in inducing normalization of US findings, whereas the secondary endpoint was to assess the effectiveness of precocious withdrawal of glucocorticoids. Methods: We prospectively enrolled all the patients with active GCA at our clinic. The inclusion criteria were clinical diagnosis of GCA; active disease; and clinical, laboratory, and US data, evaluated using the halo count (HC) and OMERACT GCA Ultrasonography Score (OGUS). Evaluations were repeated at 3, 6, and 12 months. Results: Twenty patients were treated with Tocilizumab and 9 with Methotrexate. All but three tocilizumab-treated patients achieved remission at six months, whereas at 12 months, all patients were in glucocorticoid-free remission. Up to three of the nine methotrexate patients experienced a lack of efficacy or minor relapses. Tocilizumab-treated patients showed a statistically significant difference between baseline and all follow-ups in terms of OGUS and HC, whereas the difference in the Methotrexate group was significant after 1 year. The mean glucocorticoid dosage significantly decreased in both groups. No severe adverse events or major relapses were reported. Conclusion: Our study demonstrates the superiority in terms of rapidity of a tocilizumab-based scheme over a methotrexate-based scheme in inducing clinical and US remission. Precocious withdrawal of glucocorticoids did not increase the risk of relapse.